Human glycolipid transfer protein domain containing 2 (GLTPD2) is a new member of the glycolipid transfer protein family (GLTP). The purpose of this study is to explore the expression and clinical significance of GLTPD2 in liver hepatocellular carcinoma (LIHC) through bioinformatics analysis. The third-party online LinkedOmics tool of TCGA database was used to analyze the relationship between GLTPD2 expression and various clinicopathological features of LIHC. Ualcan tool was used to analyze the mRNA expression of GLTPD2 in LIHC. Kaplan-Meier Plotter database, GEPIA data and Oncolnc database were used to evaluate the effect of GLTPD2 on survival in LIHC, and Timer 2.0 database was used to analyze the correlation between GLTPD2 and tumor immune cell invasion level. Metascape conducted functional enrichment analysis of GLTPD2 and its co-expressed genes, and predicted its biological function, and constructed and used for LIHC cancer prognosis. The results showed that GLTPD2 expression was low in LIHC, and affected the clinicopathological features, immune cell infiltration level, survival rate and prognosis of patients with LIHC. GLTPD2 is abnormally expressed in LIHC and is closely related to the initiation and progression of LIHC, which may be used as a potential biomarker of LIHC, and was of important implication for the early diagnosis, gene targeted therapy and prognosis evaluation of LIHC.